It is proposed to use phospholipid vesicles (liposomes) as "carriers" for introducing pharmacologically active compounds into cells both in vitro and in vivo. Recent evidence indicates that lipid vesicles are taken up avidly by cultured cells in vitro. Furthermore, it seems probable that an important route for cellular incorporation is fusion of the vesicles with the plasma membrane of the cell. The contents of the vesicle will thus be free to diffuse into the cytoplasm following such mechanism of incorporation. We plan to use drug-containing lipid vesicles to enhance the cellular incorporation of several chemotherapeutic agents that are not taken up normally by living cells or have very short plasma half-life in vivo. We will incorporate drugs into vesicles, characterize their uptake in vitro and assay their biological effects. We will study, in vivo, the rate of clearance of different vesicles from the blood, their distribution in different tissues and any anti-tumor effects. The composition and size of the vesicles will be varied in order to obtain maximal drug sequestration and minimal leakage, and optimal plasma clearance rate, uptake by cells and tissue distribution. In adition we will investigate the possibility of making vesicles specifically targetted to specific cell types and tissues.